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The mucopolysaccharidoses are a clinically heterogeneous group of lysosomal
storage disorders presenting with broad multi-system disease and a continuous range of
phenotypes. Currently there are no objective biomarkers of MPS disease that clearly
reflect disease severity or therapeutic responsiveness. Using proteomic studies in the
murine MPS I model, I have identified the formation of the heparin cofactor II-thrombin
(HCII-T) complex, a well-known serine protease inhibitor (serpin)-serine protease
complex, as an informative biomarker for MPS I. MPS I patients showed a range of
serum HCII-T concentrations from 16,300 - 208,600 pM, whereas the control values
varied from 38.94 - 1491 pM. HCII-T complex was also elevated in plasma from MPS I
patients and mice. The degree of HCII-T complex formation appears to correlate with
disease severity and is responsive to therapy. In addition to its role as a biomarker, the
discovery of increased serpin-serine protease complex formation provides a valuable
insight into possible pathophysiological mechanisms of MPS disease.